Haemophilus ducreyi is the etiologic agent of chancroid, a common genital ulcer disease in developing countries. To figure out how H ducreyi causes disease, we developed a human challenge model of H ducreyi infection. We have safely infected 28 volunteers on the skin of the upper arm at a total of 69 sites with doses ranging from 15 to 1,000,000 germs. Hemolysins are toxins produced by bacteria. H ducreyi makes a hemolysin. We recently inactivated the hemolysin gene and made a mutant H ducreyi that can't make the hemolysin. H ducreyi kills human skin cells grown on plates, while the mutant does not kill the skin cells. In rabbits, the hemolysin mutant caused disease that was similar to the parent bacteria, except that the mutant initially caused more redness at the injection site than the parent. The doses of bacteria used in the rabbit model are much higher than those used in the human model. We are not sure whether these findings have meaning for human infection. H ducreyi infection makes it easier for people to infect each other with the HIV virus. The skin ulcer caused by H ducreyi makes it easier to give HIV to another person or get HIV from another person. Information obtained from this study will help determine whether the hemolysin helps cause the ulcer.